No 'Door-to-Diuretic Time' Survival Benefit Seen in Acute HF

March 28, 2018

A large cohort study has provided no support for the idea that a shorter "door-to-diuretic time" in acute heart failure (AHF) may lead to better clinical outcomes, a concept with some appeal that has been variously supported and disputed in earlier studies.

Whether intravenous (IV) diuretics were initiated within 60 minutes of emergency department (ED) arrival or later than 60 minutes made no difference to the primary endpoints of death during hospitalization or a month or a year after discharge.

The findings, based on more than 2700 patients participating in the prospective, multicenter Korea Acute Heart Failure (KorAHF) registry, were much the same in several different adjusted analyses.

Timely initiation of diuretics in the hospital is a worthy goal if only to alleviate symptoms sooner, but achieving it earlier won't improve survival, and there are reasons not to unduly rush it, observed Dong-Ju Choi, MD, Seoul National University, Republic of Korea, for | Medscape Cardiology.

For example, "Dyspnea is a common complaint, but heart failure is not always the cause for all dyspneic patients," he said in an email.

"The physicians may have more time to make accurate diagnosis with a proper physical examination and laboratory tests, instead of being 'rushed' into rapid initiation of diuretics without definite diagnosis," said Choi, who is corresponding author on the study, published March 26 in JACC: Heart Failure with lead author Jin Joo Park, MD, also from Seoul National University.

However, it remains controversial whether AHF can have acute harmful effects that are worth addressing early with diuretics and vasodilators.

In particular, the observational REALITY-AHF study had methods and endpoints similar to those of the current study, and it too involved an East Asian cohort, which Choi acknowledged had a similar risk profile. Yet it saw an in-hospital survival advantage with earlier initiation of IV diuretics.

Still, the KorAHF researchers and other groups take the view that AHF represents a peak in a protracted course lasting days or weeks. "We believe AHF is a 'subacute' process with a remote trigger, followed by successive hemodynamic and clinical congestion, which can be reversed with diuretic therapy. There is a relatively long time interval between the trigger and full-blown acute heart failure," Choi said.

Therefore, the findings suggest that "the length of door-to-diuretic time on clinical outcomes in patients with acute heart failure has a limited role for in-hospital and postdischarge outcomes."

An editorial accompanying the report essentially agrees, additionally noting that "decompensation is a heterogeneous and incompletely understood process driven to various degrees by myriad underlying pathobiologic mechanisms that differ widely between patients."

Moreover, AHF "remains a clinical and potentially challenging diagnosis in many patients, without a single 'gold standard' diagnostic test," write G Michael Felker, MD, Duke University School of Medicine, Durham, North Carolina, and James L Januzzi Jr, MD, Massachusetts General Hospital, Boston.

"Thus it is possible that acute therapy for heart failure may actually be too early (i.e., patients may be treated early for heart failure but may turn out to have another diagnosis, such as pneumonia or pulmonary embolus)," they write.

"Although it certainly stands to reason that prompt diagnosis and initiation of therapy are part of efficient clinical care, the overriding consideration should remain 'get it right' rather than 'do it fast.'"

Of the 2761 patients in the analysis, 24% started on IV diuretics within 60 minutes of ED arrival and the remaining 76% began treatment after more than 60 minutes; the median was 128 minutes. Women made up about half the total cohort, and 55% were receiving a heart failure diagnosis for the first time.

Overall in-hospital mortality was 5.1%; among patients surviving to discharge, mortality was 3.1% at 1 month and was 18.6% at 1 year.

There were no significant differences in the three mortality endpoints between those starting on IV diuretics up to 60 minutes after ED arrival vs later than 60 minutes.

That was true in univariate and multivariate analyses and in analyses with propensity-score matching or adjustment for Get With The Guidelines Heart Failure (GWTG-HF) risk score.

Kaplan-Meier curves for hospitalization due to worsening heart failure did not differ significantly at 1 year.

There can be many reasons a patient with AHF might be started on diuretics later rather than earlier, Choi pointed out. In the current cohort, higher GWTG-HF risk scores and the presence of ischemic heart disease predicted later initiation of diuretics.

"We assume that since the diagnosis of acute heart failure is not always easy, and in case of 'stable' AHF, the physicians may have performed more diagnostic tests, which are time consuming," he said.

On the other hand, those started early were more likely to have NYHA class IV dyspnea and lung congestion on radiography, which "might have alerted clinicians to earlier diagnosis and initiation of diuretics."

Choi, Park, their coauthors, and Felker and Januzzi report that they have no relevant relationships to disclose.

JACC Heart Fail. 2018;6:286-294, 295-297. Abstract, Editorial

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